Meniere's Disease is one of the pathological entities characterized by endolymphatic hydrops of the cochlear and vestibular labyrinths. Hydrops can result from an alteration of ion transport properties of the epithelial cells bordering the endolymphatic system. Little is known about the cellular basis of the pathologic processes involved because data are lacking from normal as well as pathological systems concerning mechanisms of secretion and absorption of ions. Endolymph is unique in that it is the only extracellular fluid in the body with a high potassium (K+) concentration and low sodium (Na+) and calcium (Ca2+) concentrations, a composition that is essential to sustain normal hearing and balance. Our understanding of transport processes in the inner ear has increased enormously over the previous periods of this award. However, two epithelial regions, Reissner's membrane (RM) in the cochlea and the semicircular canal ducts (SCCD) in the vestibular labyrinth, make important contributions to the homeostasis of endolymphatic fluid composition and volume, but our understanding of their functions lags behind that of other cell types in the ear. It is proposed to study the transport processes responsible for fluxes of the ions K+, Na+, CI-, HC03-, Ca2+ and water in the vestibular labyrinth and cochlea by RM and SCCD. These investigations will utilize our established microdissection, electrophysiologic, molecular biologic and immunohistochemical techniques as well as novel extensions of these (cochlear slice preparation to better preserve function of delicate tissues during isolation, conductance scanning to study paracellular transport pathways, fluctuation analysis of epithelial currents to determine ion channel properties and RNA inhibition to knock down the expression of specific genes). The experimental design will test a series of hypotheses about RM and SCCD transport that will lead to an understanding of fundamental, key roles of these epithelia in the health and disease of hearing and balance.